How to predict nephropathy in type 1 diabetic patients

OBJECTIVE: Do exaggerated increases in blood pressure and albuminuria during exercise occur earlier than microalbuminuria and which type of test is most predictive of diabetic nephropathy? MATERIAL AND METHODS: A total of 33 insulin-dependent normoalbuminuric men (mean duration of diabetes 14 years; mean age 28 years) and 34 age-matched apparently healthy control subjects were studied. Urinary albumin excretion, heart rate and blood pressure were measured during fixed workload (150 W) and fixed heart rate (155 beats/min) tests. Mean follow-up time was 13.1 +/- 3.2 years. A urinary albumin level in early-morning urine persistently >30 mg/l was considered a sign of diabetic nephropathy. RESULTS: Sixteen patients reached the endpoints of the study. Eleven had developed microalbuminuria and five macroalbuminuria (persistent levels of urinary albumin >300 mg/l). Of the latter patients, two needed dialysis. Systolic blood pressure and albumin excretion during the fixed heart rate test were higher in diabetic patients who developed signs of nephropathy than in control subjects and diabetic subjects with persistent healthy kidneys. Such differences were not found in the fixed workload test. There were no differences in glycated haemoglobin, blood pressure levels or albumin excretion at baseline between the two diabetic groups. CONCLUSIONS: To predict the development of diabetic nephropathy it seems important to choose a fixed heart rate test. High levels of systolic blood pressure in such a test were associated with the development of micro- and macroalbuminuria.     

Abnormal albuminuria and blood pressure rise in incipient diabetic nephropathy induced by exercise

The aim of the study was to evaluate the influence of light to moderate dynamic work (450 kpm/min followed by 600 kpm/min during 20 min each) on the blood pressure and renal protein handling in insulin-dependent diabetic patients with incipient nephropathy (D3) (elevated baseline albumin excretion but without clinical proteinuria). Fifteen male diabetic patients (D3) with a mean age of 26.5 +/- 4.8 years (SD) and a diabetes duration of 15.6 +/- 3.4 years (SD), 11 comparable diabetic patients with normal urinary albumin excretion (D2), and ten non-diabetic subjects (C) were studied. In D3 baseline diastolic blood pressure was elevated [92.1 mm Hg +/- 6.0 (mean +/- SD)] compared to D2 (80.9 mm Hg +/- 4.8, 2P = 0.003%) and C (79.5 mm Hg +/- 12.4, 2P = 1.2%). Baseline systolic blood pressure was not significantly different in the three groups, but systolic blood pressure was more elevated at 600 kpm/min in D3 (193.0 mm Hg +/- 23.0) compared to D2 (170.5 +/- 17.3, 2P = 1.2%) and C (157.5 mm Hg +/- 20.9, 2P = 0.07%). Baseline albumin excretion in D3 was 82.6 micrograms/min X/ divided by 2.5 (geometric mean X/ divided by tolerance factor) and during exercise the maximal albumin excretion rose to 195.0 micrograms/min X/ divided by 2.6 (2P = 0.01%). In D2 albumin excretion rose from 3.3 micrograms/min X/ divided by 1.9 to 7.9 micrograms/min X/ divided by 1.5 (2P = 0.02%). The albumin excretion in C did not change during exercise. A highly significant correlation between maximal exercise induced systolic blood pressure and maximal exercise induced albumin excretion was demonstrable in D3.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study of Tamm-Horsfall protein excretion in hypertensive patients and type 1 diabetic patients.

OBJECTIVE: The study was performed in order to evaluate to what extent hypertension or diabetes mellitus may affect the urinary excretion rate of Tamm-Horsfall protein. MATERIALS AND METHOD: The urinary excretion rates of albumin and Tamm-Horsfall protein, a measure of glomerular and distal tubular function, respectively were measured in patients with essential hypertension (n = 17) and in type 1 diabetes with (n = 20) or without nephropathy (n = 8) and in apparently healthy subjects (n = 10). RESULTS: Mean 24-h ambulatory blood pressure measurements showed higher blood pressure levels in the hypertensive (167/ 106 mmHg, p < 0.001) than in the diabetic patients with (136/84 mmHg) and without nephropathy (121/74 mmHg) and in healthy subjects (122/76 mmHg). Day and night ratios of systolic and diastolic blood pressure levels were not different among the four groups. Urinary albumin excretion rate was increased in patients with hypertension (30.8 x/ 3.4 microg/min; geometric mean x/tolerance factor; p < 0.001) and diabetes with nephropathy (462 x/ 3.5 microg/min; p < 0.001) compared with diabetic patients without nephropathy and healthy subjects (4.6 x/ 1.9 and 3.7 x/ 1.5 microg/min, respectively). The Tamm-Horsfall protein excretion rate was decreased in patients with diabetic nephropathy (11.6 x/ 3.5 microg/min) compared to patients with hypertension (36.3 x/2.1 1g/min; p < 0.01), diabetes without nephropathy (39.2 x/ 2.0 microg/min; p < 0.05) and healthy subjects (63.0 x/ 1.4 microg/min; p < 0.001), whereas no differences were found among the latter three groups. CONCLUSION: These data indicate that high blood pressure may be associated with albuminuria, while a decrease in excretion rate of Tamm-Horsfall protein may be associated with diabetic nephropathy. These associations need to be studied in a larger population.     

Relationship between urinary albumin excretion and glomerular filtration rate in normotensive, nonproteinuric patients with type 2 diabetes mellitus

BACKGROUND/AIM: In patients with type 2 diabetes mellitus, the relationship between glomerular filtration rate (GFR) and urinary albumin excretion remains an unresolved issue. In order to investigate the early renal function abnormalities, GFR and urinary albumin excretion were assessed, and their relationship was examined in normotensive patients with type 2 diabetes mellitus. METHODS: In a cross-sectional study of 85 nonhypertensive Japanese patients with type 2 diabetes mellitus not showing overt proteinuria, the GFR was measured using (99m)Tc-diethylenetriamine pentaacetate renography. Fifty-one diabetic patients lacked microalbuminuria (albumin excretion <30 mg/day), while 34 patients showed microalbuminuria (between 30 and 300 mg/day). Fifteen healthy subjects served as controls. RESULTS: The three groups were well matched with regard to gender, age, and body mass index. The GFR in microalbuminuric patients (134 +/- 23 ml/min/1.48 m(2)) was significantly higher than in patients without microalbuminuria (108 +/- 21 ml/min/1.48 m(2)) and in controls (109 +/- 18 ml/min/1.48 m(2); p < 0.0001). In type 2 diabetic patients, the GFR positively correlated with the logarithmically transformed urinary albumin excretion. Multiple regression analysis showed that the urinary albumin excretion was significantly and independently affected by GFR (beta = 0.548), duration of diabetes (beta = 0.297), and systolic blood pressure (beta = 0.232; R(2) = 0.409; p < 0.0001). CONCLUSION: It is suggested that one of the mechanisms underlying increased urinary albumin excretion in early nephropathy in normotensive type 2 diabetes is glomerular hyperfiltration.     

Postexercise albuminuria in children with different duration of type-1 diabetes mellitus

. About 30% of diabetic patients develop progressive renal failure. We studied albumin, IgG, and transferrin excretion during exercise in diabetic children without signs of nephropathy to investigate proteinuria under these conditions: 39 patients with insulin-dependent diabetes mellitus and 21 healthy children undertook a bicycle exercise test. Albuminuria measured by nephelometry was calculated as the albumin excretion rate (AER) and albumin-to-creatinine ratio before and after exercise. The diabetic group was divided into three subgroups according to disease duration (DI<5 years, DII 5 – 10 years, DIII>10 years). No significant difference in metabolic control (hemoglobin A_1c) was detected between the diabetic groups (median hemoglobin A_1c: DI 7.2%, DII 7.6%, DIII 8.6%). There was no increase in AER in the healthy children after exercise. Before exercise the diabetic groups had an AER similar to controls. No significant increase in albuminuria after exercise was seen in group DI. Both groups with a disease duration of more than 5 years had a significant increase in albuminuria [median before/after: DII 7.8/16.7 (P< 0.05), DIII 0/57.9 (P< 0.05) μg/min per 1.73 m²). Of these patients, 43% also had a measurable urinary excretion of IgG and transferrin, indicating structural glomerular damage. There was no correlation of albuminuria and parameters of metabolic control or renal function. We conclude that in diabetic children an exercise test unveils albuminuria in certain patients, while their AER may be normal at rest. Received September 22, 1995; received in revised form and accepted January 24, 1996     

Increased glomerular filtration rate as a predictor of diabetic nephropathy--an 8-year prospective study.

The objective was to study the natural history and the predictive value of glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c for diabetic nephropathy. A cohort of 75 type-1 diabetic adolescents with a diabetes duration of 8 years was studied. Thirty-one females, 33 males, mean age 16.9 +/- 0.3 (SEM) participated in the follow-up study. Glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c were measured every second year during 8 years to determine the predictive value of glomerular filtration rate for future nephropathy. Initial differences and patterns of changes in glomerular filtration rate, albumin excretion rate, and hemoglobin A1c were examined in patients who did (group 1) and did not (group 2) develop incipient or overt nephropathy. Five of 64 patients developed overt nephropathy. They had an initial glomerular filtration rate of greater than 125 ml/min/1.73 m2. Fifteen of 53 initially normoalbuminuric patients developed incipient and three of 53 overt nephropathy. Age, age at onset, diabetes duration, initial albumin excretion rate, initial blood pressure, and hemoglobin A1c were similar in groups 1 and 2. Glomerular filtration rate was initially higher in group 1 than in group 2 (P = 0.01). The positive predictive value for combined incipient and overt nephropathy of an initial glomerular filtration rate greater than 125 ml/min was 53%. The negative predictive value of glomerular filtration rate less than 125 ml/min was 95%. In initially normoalbuminuric patients multiple regression revealed initial glomerular filtration rate as the only significant independent predictor for nephropathy when also corrected for hemoglobin A1c (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ambulatory blood pressures and autonomic nervous function in normoalbuminuric type I diabetic patients

Background. In insulin-dependent diabetes mellitus (IDDM) patients with normal urinary albumin excretion (UAE) controversy exists about the presence of blood pressure (BP) elevation and an attenuation of BP decline during sleep. Subjects and methods. These issues were studied in 60 IDDM patients and 55 healthy control subjects with 24 h ambulatory blood pressure monitoring. In addition, in the IDDM patients two cardiovascular reflex tests were performed to study autonomic nervous function. Results. 55 IDDM patients had 4.4/3.1 mmHg higher 24 h systolic/diastolic pressures when compared with 55 healthy matched controls (P=0.005/0.009). The diastolic BP decline during sleep was significantly attenuated in IDDM patients compared to healthy volunteers (18.9 vs 22.2%, P=0.01). The maximum/minimum (max/min) ratio of the RR′ interval of the lying to standing test (lower values indicating (incipient) parasympathetic dysfunction) was positively related to the decline of the diastolic BP during sleep in the diabetic patients. This relationship did not persist after adjusting for decline of heart rate during sleep. Conclusions. IDDM patients with normal UAE, compared with healthy control subjects, have higher BPs during both the waking and sleeping periods and a decreased diastolic BP decline during sleep. In these patients both the diastolic BP decline and the heart rate decline during sleep were related to the max/min ratio. These findings are consistent with the hypothesis that attenuation of diastolic BP decline during sleep is at least partly due to (incipient) damage to the parasympathetic nervous system, which, through a blunted heart rate decline, leads to a decreased decline of cardiac output during sleep.     

Urinary sulphated glycosaminoglycans and Tamm-Horsfall protein in type 1 diabetic patients

OBJECTIVE: In diabetic nephropathy there is a decrease in glycosaminoglycans (GAG) in basement membranes and in Tamm-Horsfall protein (THP) in the distal tubules of the kidneys. Since GAG is present in both glomerular and tubular basement membranes, and the synthesis of both GAG and THP involves glycosylation, this study was carried out in order to investigate whether urinary excretion of these substances is interrelated. MATERIAL AND METHODS: 24-h urinary collections were analysed. A total of 94 diabetic patients were grouped in accordance with the urinary albumin excretion rate as normo- (<20 microg/min) (n = 35), micro- (20-200 microg/min) (n = 30) and macroalbuminuria (>200 microg/min) (n = 29). RESULTS: In comparison with 26 control subjects, the excretion rate of GAG was decreased in patients with micro- and macroalbuminuria and excretion of Tamm-Horsfall protein in patients with macroalbuminuria. The excretion rates of GAG and THP were associated (r = 0.64, p < 0.001) and correlated with creatinine clearance (r= 0.46 and r= 0.53, p < 0.001; respectively) but not with levels of HbA1c. CONCLUSIONS: In conclusion, albuminuria was associated with decreased urinary excretion of sulphated GAGs, which was associated with the excretion rate of Tamm-Horsfall protein, indicating that excretion of GAG was associated with distal tubular dysfunction in diabetic patients.     

Short-term administration of captopril and nifedipine and exercise-induced albuminuria in normotensive diabetic patients with early-stage nephropathy

Recent studies have demonstrated that short-term angiotensin converting enzyme (ACE) inhibition with captopril can reduce urinary albumin excretion rate (UAER) after exercise in normotensive diabetic patients with early-stage nephropathy. The aim of this study was to investigate whether this effect of ACE inhibition was due to a systemic hypotensive action or a specific action at the intrarenal level. Thus, we compared the acute effects of captopril and the Ca2(+)-channel blocker nifedipine on exercise-induced UAER in normotensive (blood pressure less than 165/95 mmHg) diabetic patients who were normoalbuminuric or microalbuminuric at rest (stage 2 or 3 of diabetic nephropathy). Twenty-five stage 2 diabetic nephropathy patients, 39 stage 3 diabetic nephropathy patients, and 12 nondiabetic subjects performed five submaximal cycloergometric exercises (90% of theoretical heart rate) on nonconsecutive days. The first two exercises were performed in basal conditions; the next three exercises were performed 24 h after administration of captopril (25 mg twice daily) or nifedipine AR (20 mg twice daily) or placebo (1 tablet twice daily) according to a randomized double-blind crossover trial. After placebo, blood pressure and UAER did not change at rest or 1 h after exercise. After captopril, blood pressure at rest and during exercise was similar to that observed after placebo. UAER at rest was not modified, whereas 1 h after exercise, it was significantly decreased both in stage 2 and stage 3 diabetic nephropathy patients (P less than 0.001). After nifedipine, blood pressure decreased significantly at rest and during exercise in respect to placebo and captopril. UAER at rest did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac hyperfunction in insulin-dependent diabetic patients developing microvascular complications

Cardiac function was studied by echocardiography in 80 insulin-dependent diabetic patients with no signs of ischemic heart disease and in 40 healthy control subjects. Echocardiographic findings were related to the urinary albumin excretion rate (UAE). In the diabetes group, fractional shortening of the left ventricle (FS) was 37.3% versus 34.3% (P less than .01) in the control group, whereas indices of preload and afterload were at the same levels as in control subjects. In diabetic patients with preclinical nephropathy (UAE 20-200 micrograms/min), FS was 41.1% compared to 37.0% (P less than .002) in patients with no signs of nephropathy (UAE less than 20 micrograms/min) and 34.8% (P less than .001) in patients with clinical nephropathy (UAE less than 200 micrograms/min). Furthermore, in patients with preclinical nephropathy, afterload was significantly decreased, whereas preload was at the same level as in the other two groups of UAE. In conclusion, a condition of cardiac hyperfunction has been found in diabetic patients with no signs of ischemic heart disease and seems pronounced in diabetic patients developing microvascular disease (patients with preclinical nephropathy), probably secondarily to a condition of hyperperfusion in these patients.     

Effects of aerobic exercise on microalbuminuria and enzymuria in type 2 diabetic patients

Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 +/- 7.3 years, with a mean BMI of 30.8 +/- 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.     

Effects of Aerobic Exercise on Microalbuminuria and Enzymuria in Type 2 Diabetic Patients

Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-β-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 ± 7.3 years, with a mean BMI of 30.8 ± 3.0 kg/m²). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.     

Urinary microRNA-29 correlates with urinary albumin in type 2 diabetes mellitus

ObjectiveTo investigate the possibility of urinary microRNA-29 (miR-29) as biomarker for diabetic nephropathy in patients with type 2 diabetes. Methods Sixty-one patients with type 2 diabetes were divided into 2 groups: diabetes with normoalbuminuria[n＝25, (58.88±11.75) years old] and diabetes with albuminuria[n＝36, (62.19±13.11) years old]. There were no significant differences in age and gender between groups. The contents of miR-29a, miR-29b and miR-29c in urine supernatant were determined by real-time quantitative PCR, and a synthetic cel-miR-39 was added to the urine as a spike-in control before miRNAs extraction. The laboratory parameters including urinary albumin excretion, serum creatinine, BUN, glycosylated hemoglobin, and blood lipids were collected, while retinopathy serves as non-invasive method to assess vascular fibrosis. Results There was no significant difference in glycosylated hemoglobin levels and duration of diabetes between two groups, while the diabetes with albuminuria group had lower estimated glomerular filtration rate (eGFR) (P＝0.001), had higher level of miR-29a, miR-29b and miR-29c in urine (P＝0.029, 0.032, 0.040) compared with diabetes normoalbuminuria group. Urinary albumin excretion rate significantly correlated with urinary miR-29a level (r＝0.284, P＝0.039) and miR-29b level (r＝0.275, P＝0.046), urinary miR-29b significantly correlated with BUN（r＝0.277, P＝0.031）in patients with type 2 diabetes. However, no correlation was found between miR-29a, miR-29b, miR-29c and other clinical parameters. Conclusion Urinary miR-29a and miR-29b correlates with urinary albumin in patients with type 2 diabetes, and it needs further exploration and evaluation for urinary miR-29 to serve as potential biomarker for diabetic nephropathy in type 2 diabetes.     

Glomerular hyperfiltration increases the risk of developing microalbuminuria in diabetic children

An elevated glomerular filtration rate (GFR) is frequently detectable in type 1 diabetic children and adolescents and in those without any other evidence of incipient diabetic nephropathy. In 1982 we detected 23 patients with hyperfiltration (GFR>140 ml/min per 1.73 m²), aged 9–15 years, with diabetes for longer than 4 years; 23 age- and sex-matched patients with diabetes of a similar duration and without hyperfiltration served as controls. Both groups were followed until March 1992, by assessing GFR every 12 months, albumin excretion rate every 6 months, blood pressure and glycated haemoglobin (HbA1) every 3 months. Dietary protein intake was similar in patients with hyperfiltration and in controls. No other drug except insulin was used throughout the study. The insulin regimen was similar in the two groups. There was no significant difference between the two groups regarding albumin excretion, blood pressure and HbA1 at the beginning of the study. Of the 23 patients with hyperfiltration, 7 developed persistent microalbuminuria (defined as an overnight albumin excretion rate >30 g/min per 1.73 m² on at least 5 consecutive measurements); 2 of these patients had overt proteinuria. Only 1 of the diabetics with normal GFR developed persistent microalbuminuria. The positive predictive value for microalbuminuria of an initial GFR>140 ml/min per 1.73 m² was 63%; the negative predictive value of an initial GFR<140 ml/min per 1.73 m² was 94%. The increase of albumin excretion rate into the microalbuminuric range precedes the elevation of both systolic and diastolic blood pressure. Persistent glomerular hyperfiltration is a risk factor for the development of microalbuminuria and incipient nephropathy in type 1 diabetic children, adolescents and young adults.     

Diurnal variation in urinary protein excretion in diabetic nephropathy

We examined the diurnal variation in urinary excretion rate of albumin, IgG and beta 2-Microglobulin (beta 2-M) in healthy volunteers (n = 24), and in patients with type I diabetes mellitus having normal albumin excretion rate (less than 20 micrograms/min; n = 16), incipient diabetic nephropathy (albumin excretion rate 20-200 micrograms/min; n = 12) and clinical diabetic nephropathy (albumin excretion rate greater than 200 micrograms/min; n = 12). Diurnal variation was defined as [(overnight minus daytime): daytime excretion rate] times 100%. Median diurnal variation in albumin excretion rate in the various groups varied from -32 to -57%, and in IgG excretion rate from -42 to -65%, being not significantly different between the proteins or between the groups. Diurnal variation in beta 2-M excretion rate was similar in healthy volunteers and in patients with normal albumin excretion rate or incipient diabetic nephropathy (median -36 to -43%), but significantly reduced in patients with clinical diabetic nephropathy (median 0%; P less than 0.005), nine of whom had elevated beta 2-M excretion rates, suggesting tubular dysfunction. Except for beta 2-M excretion rate in patients with clinical diabetic nephropathy, the diurnal variations in albumin excretion rate, IgG excretion rate and beta 2-M excretion rate were larger than the diurnal variation in creatinine excretion rate (median -7 to -11%, P less than 0.005). Diurnal variations in albumin excretion rate and IgG excretion rate were highly correlated (r = 0.89, P less than 0.00001). These data suggest that similar mechanisms may account for diurnal variations in albumin excretion rate and IgG excretion rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Performing only one cardiovascular reflex test has a high positive predictive value for diagnosing autonomic neuropathy in patients with chronic renal failure on hemodialysis

BACKGROUND: Autonomic neuropathy is an important cause of morbidity and mortality in patients with chronic renal failure (CRF) on hemodialysis. Generally, cardiovascular reflex tests are used to determine autonomic neuropathy. Our purpose in this study was to determine the frequency of autonomic neuropathy in patients with CRF on hemodialysis by using cardiovascular reflex tests and compare the sensitivity of each test. METHODS: The authors performed five tests: heart rate response to the Valsalva maneuver, heart rate variation during deep breathing, heart rate response to standing up, blood pressure response to standing up, and blood pressure response to hand grip exercise in order to determine autonomic neuropathy. Each test subject was evaluated as normal, borderline, and abnormal and scored as 0, 1, and 2, respectively. Subjects with a total score > or = 5 were considered to have autonomic neuropathy. Forty subjects with CRF on hemodialysis were included in this study. None of the subjects had diabetes mellitus or any other etiology that could cause autonomic neuropathy. RESULTS: Thirty-five of 40 subjects (87.5%) had abnormal autonomic tests. In 35 subjects, the relationship between autonomic neuropathy and biochemical parameters, effects of treatment with vitamin D and erythropoietin, and urea reduction rate were studied. No relationship was found between autonomic neuropathy and age, time on hemodialysis, urea reduction rate, albumin, ferritin, calcium, inorganic phosphorus, intact parathyroid hormone, hemoglobin levels, and treatment with vitamin D and erythropoietin. The abnormal test results were as follows: 20 subjects (50%) in the heart rate response to the Valsalva Maneuver, 31 (77.5%) in the heart rate variation during deep breathing, 28 (70%) in the heart rate response to standing up, 6 (15%) in the blood pressure response to standing up, and 31 subjects (77.5%) in the blood pressure response to hand grip exercise tests. Among these five tests, the two most abnormal tests were the heart rate variation during deep breathing and the blood pressure response to hand grip exercise. CONCLUSION: Patients with CRF on hemodialysis frequently have autonomic neuropathy. For the diagnosis and follow-up of patients, five cardiovascular autonomic reflex tests are generally used. In this study, it was determined that performing only one test instead of all five tests has a high sensitivity and is more practicable in terms of determining autonomic neuropathy.     

No microalbuminuria or other adverse effects of long-standing hyperfiltration in humans with one kidney

Hypertrophy and hyperfiltration are characteristic features of single kidneys and kidneys of patients with insulin-dependent diabetes mellitus (IDDM). In both cases the hyperfiltration has been suggested to be involved in the pathogenesis of renal functional deterioration. We studied the effect of long-standing hyperfiltration on kidney function in 29 subjects with one kidney, three of whom were insulin-dependent diabetics. Four groups were studied: (1) uninephrectomized less than 10 years since uninephrectomy (UN) (n = 7; age, 30 +/- 6 years); (2) uninephrectomized greater than or equal to 10 years since UN (19 +/- 11 years, 10 to 52); n = 14; age, 38 +/- 15 years; (3) congenital unilateral renal agenesis (n = 5, age, 39 +/- 16 years); and (4) IDDM patients with one kidney (n = 3; age, 28 to 52 years; diabetes duration, 8 to 31 years; years with one kidney, 18 to 30). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique, kidney volume (KV) by ultrasonic scanning, and urinary albumin excretion rate (UAE) by radioimmunoassay. In all subjects GFR, RPF, and KV were within the normal range, representing a single kidney hyperfiltration of approximately 70% and hypertrophy of approximately 100%. Only one of the subjects with renal agenesis had an elevated UAE (117 micrograms/min); the remainder had a normal UAE, ie, less than 10 micrograms/min, and the diabetics were below the risk level of 20 micrograms/min. Serum creatinine was normal and BP was slightly elevated in only three subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of 24-h cardiac parasympathetic activity and degree of nephropathy in IDDM patients.

In insulin-dependent diabetic patients, nephropathy is a predictor of mortality and coronary heart disease. Impaired cardiac vagal function is an important factor in the pathophysiology of sudden cardiac death in coronary heart disease. Autonomic neuropathy in diabetes in particular involves vagal function. Bedside tests and 24-h measurements of cardiac parasympathetic activity were compared in 37 insulin-dependent diabetic patients, and the relationship between 24-h vagal activity and degree of nephropathy was investigated. Nephropathy was classified according to urinary albumin excretion as normoalbuminuria, incipient, and overt nephropathy. Mean age (approximately 30 yr) was not different among groups. The 24-h measurements of parasympathetic activity appeared more sensitive than bedside tests, as 33% of patients without cardiac autonomic neuropathy in bedside tests had 24-h vagal activity values below the 95% confidence limits of 14 healthy control subjects. Patients with incipient or overt nephropathy had significantly lower mean values for vagal activity during both wake and sleep time than healthy control subjects. Increasing degree of nephropathy was associated significantly with increasing attenuation of 24-h vagal activity (P less than 0.001). The covariation of degree of neuropathy and nephropathy may suggest common pathogenetic mechanisms. The reduced 24-h vagal activity, even in the early stages of nephropathy, could be an important risk factor for cardiac death in insulin-dependent diabetic patients.     

Kidney hemodynamics after ketone body and amino acid infusion in normal and IDDM subjects

Little information is available on the hemodynamic response (renal reserve) of the diabetic kidney during an acute amino acid infusion, which has been shown to increase glomerular filtration rate (GFR) in normal humans. We recently found that the infusion of ketone bodies is able to raise GFR in both normal subjects and insulin-dependent diabetes mellitus (IDDM) patients. The aim of this study was to evaluate the renal reserve in 15 IDDM patients with a duration of diabetes of greater than 9 yr [8 with albumin excretion rate less than 15 micrograms/min (group 1) and 7 with albumin excretion rate greater than 100 micrograms/min (group 2)] and in 8 normal subjects during amino acid infusion (33 mumol.kg-1.min-1, Travasol 10% wt/vol solution containing 0.154 mM sodium chloride concentration; Travenol, Savage, MD) and during acetoacetic sodium salt (25 mumol.kg-1.min-1) infusion. Blood glucose was clamped at euglycemic levels. The infusion of sodium acetoacetate resulted in a 10- to 15-fold increase in circulating concentrations of ketone bodies, which were similar in magnitude in normal subjects and diabetic patients. The GFR peak increase above baseline after sodium acetoacetate infusion was 28% in normal subjects and 27% in group 1 and 19% in group 2 diabetic patients. The infusion of amino acid solution produced a three- to fivefold increase in plasma concentrations of amino acids in both normal subjects and diabetic patients. The GFR peak increase above baseline after amino acid infusion was significantly lower in diabetic patients (IDDM group 1: 5%, P less than .01; IDDM group 2: 6%, P less than .01) than in normal subjects (38%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations of blood pressure in type 1 diabetic children and adolescents

The aim of this study was to assess the association between metabolic control, microalbuminuria, and diabetic nephropathy with ambulatory blood pressure monitoring (ABPM) in normotensive individuals with type 1 diabetes mellitus (DM). ABPM was undertaken in 68 normotensive type 1 diabetic patients with a mean age of 14.4+/-4.2 years. Microalbuminuria was diagnosed on the basis of a urinary albumin excretion rate grater than 20 microg/min in two of the three 24-h urine collections. Hypertension (HT) frequency was greater in the microalbuminuric patients than normoalbuminuric patients (54 vs 17.54%, p=0.05) with ABPM. Microalbuminuric patients had a higher diastolic pressure burden than normoalbuminuric patients. There were no differences in systolic and diastolic dips between the two groups. Diastolic pressure loads in all periods showed a significant correlation with duration of diabetes, mean HbA1c from the onset of diabetes, and level of microalbuminuria. Nocturnal dipping was reduced in 41.2% of the patients. In the normoalbuminuric group 41.1% and in the microalbuminuric group 63.6% were nondippers. Our data demonstrate higher 24-h and daytime diastolic blood pressure load and loss of nocturnal dip in type 1 diabetic adolescents and children. High diastolic blood pressure burden in diabetic patients could represent a risk for nephropathy.